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While both direct viral infection and systemic effects are implicated, the role of renal microthrombosis remains poorly defined in COVID-19 and AKI. Angiopoietin-2, a pro-inflammatory cytokine, and cleaved thrombomodulin is elevated in plasma in severe COVID-19 and has been linked to endothelial dysfunction and hypercoagulability. We hypothesize that renal microthrombi can contribute to decreased kidney function in critically ill COVID-19 patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We performed histopathological and molecular analyses of postmortem kidney tissue from seven critically ill COVID-19 patients. Control tissue was obtained from nephrectomy specimens (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20096) and postmortem tissue (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20097). We assessed microthrombi, tubular necrosis, glomerulosclerosis, fibrosis, and expression of angiopoietin-2 and thrombomodulin. Immunofluorescence and SARS-CoV-2 nucleoprotein staining were used alongside clinical data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      AKI was observed in six of seven COVID-19 patients. Compared to controls, COVID-19 kidneys showed a significant reduction in tubular nuclear area (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0003), presence of viral antigen in tubular epithelium, and marked glomerular and peritubular microthrombi (15.2 vs. 1.3 thrombi\/mm\u00b2;\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001). THBD expression was significantly reduced bith peritubular capillaries and glomeruli in COVID-19 kidneys. Glomerulosclerosis, glomerular area, and tubulointerstitial fibrosis were variable in both control and COVID-19 patients with no significant differences.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study identifies widespread renal microthrombi, tubular necrosis, and reduced THBD expression in COVID-19 patients with AKI, supporting a role for endothelial dysfunction and microvascular thrombosis in COVID-19-associated renal injury. The data implicates the disruption of endothelial anticoagulant signaling through thrombomodulin as a contributing mechanism.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12882-026-04788-2","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T15:36:19Z","timestamp":1769873779000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Renal microthrombosis and thrombomodulin deficiency in COVID-19\u2013associated acute kidney injury"],"prefix":"10.1186","volume":"27","author":[{"given":"Matilda","family":"Bekhet","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Marks-Hultstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00fcl Gizem","family":"Korkut","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelina","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaakko","family":"Patrakka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Englund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Jeansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,31]]},"reference":[{"issue":"1","key":"4788_CR1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1186\/s13054-022-04086-x","volume":"26","author":"H Schaubroeck","year":"2022","unstructured":"Schaubroeck H, Vandenberghe W, Boer W, Boonen E, Dewulf B, Bourgeois C, Dubois J, Dumoulin A, Fivez T, Gunst J, et al. 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